Patient #12 looks like it could be another CR in the making and the one for patient #7 looks durable. If we get another CR in the trial (2/15), that is probably not chance, especially considering the antigen spreading response data in responding patients.

Yep. That sums things up nicely. I will add that marker for its MC has one thing that the great majority of I-O biotechs this size don't have. Lots of CRs. The treatment is active with no side effects of consequence. How often has that happened before with cancer treatments? Never.

Yes. Yes. Yes. They should partner. Complimentary technologies. CAR-T/NK is like shooting a bullet, Multi-TAA is like shotgun pellets. If you want to make sure you kill the tumor, use both.

I think we're here because the science is just not as sexy as multi-edited CAR-T. However, multi-TAA actually seems to work and the 2 treatments are not mutually exclusive. This is one of those biotechs that will not rise on hype. It must show more proof of activity until it can simply not be dismissed.

What are you talking about?

In the presentation PH made the new claim that PC responses "correlated perfectly" with patients who demonstrated epitope spreading. Prior to this claim they had only shown epitope expansion had occurred in some responding patients but did not correlate responses with epitope expansion (i.e it might have otherwise occurred in all patients and had no impact on tumor response). If what he claimed is true, this strongly suggests cause and effect and, thus, activity of multi-TAA in PC in the context of chemotherapy.
Furthermore, he claimed 9/15 CRs in the lymphoma group with no relapses. That again, if true, is amazing, especially for a non toxic treatment. In the presentation on the website I did not see this high # of CRs, so either PH is wrong or more CRs have occurred and this is new. Please correct me if I'm wrong here.

yep. I'd say that sums up biotech investing pretty well. You have to do a ton of research to come out ahead. Then you need a bit of luck as well.

Your point is excellent. Furthermore, multi-TAA has cured patients of resistant hematologic cancers. Something is amiss here. Either the company is a total fake or the selling is way way overdone for a failed ovarian cancer trial and a technical delay in starting a Multi-TAA trial. Multi-TAA is the one and only reason I invested here. Vaccines have a dismal record in I-O. The AML trial will proceed as we already know Multi-TAA is safe. Unless our management is totally incompetent, they should be able to resolve the issue quickly.

I have said if the results aren't fabricated, the company is way undervalued and is a screaming buy at this point. Personally, I have never seen fabrication of clinical results by a biotech company, but I suppose there are examples. More prone to occur with preclinical studies. That said, CRs are CRs and I think someone would end up in jail if what Balyor clinicians have reported is not real.
No - I don't think the data is fabricated and, yes, I think MRKR is way undervalued at this price. I bought more yesterday and will continue adding if it goes down further.
I think it's reasonable to expect a major partnership here. Multi-TAA is the perfect adjuvant treatment. It's active in multiple cancers and it is not physiologically or financially toxic. Just my opinion.

I'm not convinced that MRKR management has its act totally together yet, however, there's no getting around the hard fact that Multi-TAA produces CRs in heavily pretreated lymphoma patients and it induces antigen.epitope spreading in both hematological and solid tumors. That was all achieved with negligible toxicity. Have any idea how rare that is in I-O or oncology in general?
The platform works and is non toxic. Period. Perfect for combination treatments. This company will either gain traction with cash infusion partnerships or get bought IMO.

The best thing MRKR has going for it is stand alone CRs in some hematologic malignancies and clear evidence of antigen/epitope spreading in hematologic and solid tumors. Now they need to start combining the treatment with other immunotherapy treatments that work such as anti-PD1 and anti-CTLA4 to go for synergism. Multi-TAA has no side effects so the combos should be as safe as the checkpoint blockers. What's the hold up? Why doesn't Baylor do this?

Thanks for sharing this information and good luck. I too would sign up for multi-TAA if I was in your situation. Stay well.

It depends. If the vaccine is producing complete regression of the in situ disease in a significant percentage of patients, it's likely not overhyped. We just don't know until we see a presentation of the data. Believe me, I want to see this work, but vaccines have a very long history of failure in I-O with the exception of those directed against tumor associated viruses. That may be about to change with checkpoint blockade combinations with vaccines. We need to keep expectations in check here until we see some real data.

I think this is interesting but a bit overhyped at this stage. They apparently saw some inflammatory markers (TILs?) in her post vaccine biopsy specimen that were not there in her original biopsy I presume. That's interesting and could translate to lower recurrence but we're not there yet. We definitely need to see some data from MRKR.
Also the question is whether checkpoint blockade would enhance this vaccination in patients with high recurrence risk.
If the vaccine consistently turns a 'cold' tumor into a 'hot' tumor, it will likely translate to real survival benefit, especially in the context of checkpoint blockade.

We did. I just don't think he was officially outed. Didn't take a genius to connect the dots though.

Ha You outed him, but today is national outing day He is the most knowledgable guy on these MBs.

Redplate should know. Check out his background from his past posts on yahoo.

PS You're right that the future is in combinations. Trick is to find combos that don't stack on toxicity. I think Multi-TAA + Darzalex would be a good choice, since we have already shown some activity in MM and Multi-TAA has no toxicity. My guess is we would see durable responses with Darzalex via the multi targeting. I would think J&J would jump on this.

Yes! Correct! J&J is even better, since MRKR is now located in the J&J incubator. I was thinking of Revlimid.

I posted this before Phantom Lord, but if I was PH, I would approach Celgene about a Darzalex/Multi-TAA trial in MM. Minimal risk, maximal response duration. Thoughts?
https://www.cancertherapyadvisor.com/home/cancer-topics/multiple-myeloma/multiple-myeloma-isatuximab-immunse-response-correlates-clinical-response/2/

Came across this today. You might want to forward to PH to get it on his radar if it is not already. Looks like Multi-TAA might be synergistic with Darzalex, based on this study showing an association of Darzalex durable response to T and B cell response to cancer testis antigens.
https://www.cancertherapyadvisor.com/home/cancer-topics/multiple-myeloma/multiple-myeloma-isatuximab-immunse-response-correlates-clinical-response/?utm_source=newsletter&utm_medium=email&utm_campaign=cta-update-hay-&cpn=gelclair_2018,verzenio122018&hmSubId=&hmEmail=kYmhJIAGqVv4gFsgxoWXLQ2&NID=1083704332&email_hash=a0bacb9c745a8ca78f87a913ae2507e6&dl=0&mpweb=1323-70785-1629733

PS They may need to go to Europe or Australia where they don't want to pay for Yescarta. Sooner the better. Get a partner and get it done. Easy to throw out ideas from the sidelines.

Thanks so much. Makes perfect sense. Of course, in a perfect world, CAR-T would be reserved for Multi-TAA failures, based on cost and durable response rates along with side effects. If i was a patient, I'd take the multi-TAA first and have the CAR-T ready to go (ideally an off the shelf product which are in development). I'm guessing that may be where this eventually ends up (maybe even both delivered together).
Thanks again for getting this info. Very reassuring!

PS I'm posting this not as a criticism, but because you seem to have some access to the CEO. Please forward this inquiry if you are able. I would love to know the answer.

PH touted the comparable response rate and better durability of response, along with absence of side effects, Vs CAR-T for lymphoma in multiple presentations. If the data is real and not cherry picked and PH has real conviction with regard to the efficacy, then this seems like a no brainer for a fast track.
What's holding it up????? We should be in an efficacy trail now or very soon based on the data already presented.
Solid tumors are tough nuts and will likely require checkpoint molecules, and lots of optimization of combinations. However, we have data that shows lymphomas are highly responsive to this treatment, so this should be moving fast at this point.

Can you explain to me why lymphoma has not been fast tracked, given all the CRs that are durable in heavily pre treated patients? What's holding that back? Why the primary focus on AML which was less responsive in patients with active disease?

We don't know what chemo he is receiving (Folfirinox vs Gem/Nab?) and we don't know what immunotherapy he is receiving. His "number" is probably CA19.9 which is correlated with disease progression. That's interesting because for Multi-TAA, we are told that CA19.9 had no correlation with response. Unfortunately the odds are simply not good with stage 4 PC, no matter who you are.

PR drops are fine. All depends on the company's goals. IMO the importance of another CR in TACTOPS
would warrant a PR

I think it's fine to trade in and out of a biotech. Buying the dips and selling the rips can work. However, the big wins occur when the company's technology works leading to a B/O or a successful commercial product. It's too easy to sell along the way, thus missing a great opportunity.
Obviously the trick is to find a relatively low MC stock with great prospects. Success is relatively rare for small biotechs, especially in I-O.
Multi-TAA, unless the data has been falsified, or cherry picked, seems to work, based on all the CRs seen in various hematological malignancies in the stand alone setting. It may also work for solid tumors, but it's just too early to be certain.
The question is will something come along that's better? Maybe, however multi-antigen targeting has a lot of intuitive appeal, both for stand alone treatment and as an adjuvant or in combinations, especially given the relatively low cost.
I have my position established here and will ride this out to see what PH can do with this seemingly powerful technology. I want to see more CRs in PC and I want to see what Multi-TAA can do when combined with checkpoint antibodies and additional antigens in the mix. They were too vague at the PC cc regarding future plans for my taste, but they may just want to play their cards close to the vest because there is competition lurking out there.

Yes. Biotechs are do rise and fall on sentiment. If your system has worked for you, fine. However, the real money is made by picking and sticking with a real winner or two. Much easier said than done and I will grant you that once the science is thoroughly understood, there's still a big element of luck because it's very difficult to predict trial results with confidence.
My point is that you can sell just when you think the top is reached based on a chart and the next day you get another CR announced in the PC trial for MRKR that could double the SP.
Channeling is a game of chicken while waiting for data announcements, which tell you the real direction of the company.

Forget your charts. The only thing that really counts here is whether Multi-TAA is killing tumors. Figure that out and you will know whether to sell, hold or add to your investment. Pretty simple really

You're correct but sometimes something as simple as saying "we hope to present data showing signs of real activity in pancreatic cancer" can send a stock soaring. It did for MRKR a couple of months ago.
CEO could say "we're continuing to see compelling evidence of activity in pancreatic cancer" (or another solid tumor) that we plan to present in an upcoming conference.
I'm just speculating and likely there's nothing new driving this, but I can't be certain. The timing is interesting.

If there is good news at the conference driving this spike, it would be nice if they would release it in a PR.

That's the only reason I contribute to the MBs, to draw out people smarter than I am and learn something.

I hope MRKR is currently or will soon combine it's treatment with anti-PD1/CTLA4. The rationale for doing so is compelling. This should enhance epitope spreading and prevent exhaustion of T-cells. More antigens, higher cell dosing and checkpoint molecules are all rational paths forward.

I particularly like the suggestion of a dose response in the pediatric cancer solid tumors. Always good to see that as a confirmation of activity, especially when not accompanied by toxicity. We obviously have along way we can push the dose. Remember, we are only taking about 100cc of blood. Easy to take more. Who knows when or if DLT will be seen.

I can't say what will happen in the IP world, but i can say that the recent JCO article showing activity for pediatric solid tumors and the Chinese article showing activity in AML is very reassuring that we're on the right track.
https://www.ncbi.nlm.nih.gov/pubmed/31356143
https://www.dovepress.com/t-cells-targeting-multiple-tumor-associated-antigens-as-a-postremissio-peer-reviewed-article-CMAR

Is she starting a company?

The patient with the CR had metastatic disease at multiple sites, including the peritoneum. This was discussed in the Q&A. The measurable target tumor (not the only tumor) was in the 1 cm range. I think tumor burden could have had something to do with the CR, however when adoptive cell therapy works, it can eliminate large tumor burden disease. There are two possibilities I see here: 1) the CR patient's tumor was more sensitive to Folfirinox. 2) Multi-TAA worked.
If we see another CR, I would conclude that Multi-TAA is working in concert with chemotherapy as CRs with metastatic pancreatic cancer are quite rare from SOC chemo and to get 2 in a cohort of 15 patients would be highly improbable just by chance.

It's a good one to hold IMO and you're not likely going to need to wait for an approval for substantial SP appreciation. Look at the price of cellular I-O companies (Allogene, Iovance, etc.). Prices rise when approvals seem more likely to the market. MRKR just needs to convince the market that the platform works and the MC should rise into the multibillion range, as with these other companies.
Frankly, I'm not sure what it will take to convince the market this is working. Maybe another CR in pancreatic cancer or a couple of more lymphoma CRs. Hard to say what will trigger the awakening.